The hormones of the female reproductive system have been implicated in breast cancer development and growth by numerous basic, clinical and epidemiological investigations. Our analysis of the available information has led to the testable hypothesis that breast cancer incidence is correlated with anovulation, that is, the incidence of menstrual cycles with adequate estrogenic but absence of progestational activity. The anovulatory hypothesis will be tested by developing and validating a comprehensive interviewer administered menstrual and reproductive history form to be used for retrospective studies of breast cancer patients treated at the University of Iowa, and matched controls. The large study of menstrual cycle length of Treloar will be employed in a prospective manner to determine whether cycles of abnormal length predispose to breast cancer. The relationship of abnormal cycle length and flat basal body temperature curve to anovulation will be tested in normal subjects of all ages by intensive reproductive hormone analysis in blood and eventually in urine. Definition of the role of sex hormones in breast cancer may permit the early identification of individuals and groups at high risk. Intervention with specific therapy to correct the hormonal disorder may prevent breast cancer development. Physiologically based judgments of the nature of the predisposing hormonal state will permit a direct attack on the neoplastic process at the level of molecular endocrinology.